DESCRIPTION (From the applicant's abstract): mtDNA deletions occur and accumulate preferentially in postmitotic, respiratory neurons and myofibers with age, and are associated with enzyme deficiencies and increased risk for cell death. The broad, long-term objectives of this application are to understand the mechanism of pathophysiology of mtDNA deletion mutations, and to what extent these mutations contribute to age-related deficits of function and atrophy of myofibers and neurons. The creation of cell lines bearing mtDNA deletions, differentiable into neurons and myotubes, is proposed, followed by the testing of the underlying mechanism by which mtDNA deletions are selected for, and the mechanism by which COX activity is decreased in mutant cells, and whether such deletions increase the risk for cell death.